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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites
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Tuning the ion selectivity of tetrameric cation channels by changing the number of ion binding sites

机译：通过更改离子结合位点的数量来调整四聚阳离子通道的离子选择性

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摘要

Selective ion conduction across ion channel pores is central to cellular physiology. To understand the underlying principles of ion selectivity in tetrameric cation channels, we engineered a set of cation channel pores based on the nonselective NaK channel and determined their structures to high resolution. These structures showcase an ensemble of selectivity filters with a various number of contiguous ion binding sites ranging from 2 to 4, with each individual site maintaining a geometry and ligand environment virtually identical to that of equivalent sites in K~+channel selectivity filters. Combined with single channel electrophysiology, we show that only the channel with four ion binding sites is K~+ selective, whereas those with two or three are nonselective and permeate Na~+ and K~+ equally well. These observations strongly suggest that the number of contiguous ion binding sites in a single file is the key determinant of the channel's selectivity properties and the presence of four sites in K~+ channels is essential for highly selective and efficient permeation of K~+ ions.
机译：跨离子通道孔的选择性离子传导对细胞生理至关重要。为了了解四聚阳离子通道中离子选择性的基本原理，我们设计了基于非选择性NaK通道的一组阳离子通道孔，并确定了其结构的高分辨率。这些结构展示了具有多个连续的离子结合位点（范围从2到4）的选择性过滤器的集合，每个单独的位置保持的几何形状和配体环境实际上与K +通道选择性过滤器中的等效位置相同。结合单通道电生理学，我们显示只有具有四个离子键合位点的通道才具有K〜+选择性，而具有两个或三个离子通道的通道则具有非选择性，并能很好地渗透Na〜+和K〜+。这些观察结果强烈表明，单个文件中连续离子结合位点的数量是通道选择性特性的关键决定因素，而K〜+通道中四个位点的存在对于K〜+离子的高度选择性和高效渗透至关重要。

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  • 作者

    Mehabaw G. Derebe; David B. Sauer; Weizhong Zeng; Amer Alam; Ning Shi; Youxing Jiang;

  • 作者单位

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040;

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040;

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040,Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040;

    Institute of Molecular Biology and Biophysics, Eidgenossiche Technische Hochschule Zurich, HPK D11, 8093 Zurich, Switzerland;

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040,Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040;

    Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040,Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9040;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    nonselective cation channel; potassium channel;

    机译：非选择性阳离子通道;钾通道;

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